This disclosure relates to formulations and methods for the controlled release of drugs, in particular the controlled release of opioids and opioid antagonists using hydrogels.
Hydrogels are materials that absorb solvents (in particular water), undergo rapid swelling without discernible dissolution, and maintain three-dimensional networks capable of reversible deformation. Hydrogels can be physically or chemically crosslinked. A number of aqueous hydrogels have been used in biomedical applications, such as soft contact lenses, wound management, and drug delivery. Hydrogels are advantageous for drug delivery as the composition of the hydrogel can often be adjusted to provide the desired release of an active agent.
Opioids are a class of analgesics used for pain management. One of the major limitations of opioid analgesics is their low therapeutic index: the toxic dose of a drug for 50% of the population (TD50) divided by the minimum effective dose for 50% of the population (ED50). There is little margin of error between an efficacious dose and a toxic dose (overdose) of an opioid. Compounding this problem is the extreme toxicity of opioids when dosage levels are too high. Opioid-induced toxicity leads to hypoventilation (respiratory depression), resulting in an increased concentration of CO2 and a decreased concentration of O2 in blood plasma. In extreme cases, when administered an overdose of an opioid, an individual can cease breathing entirely. Opioid antagonists, such as naloxone, naltrexone, nalmefene, and nalorphine, can be used to block the effects of opioids, reversing respiratory depression and other symptoms of opioid overdose. While opioid antagonists are effective, it is important to know when such administration is required, and preferably, before the individual is suffering from the physiological effects of an overdose.
In addition to use in clinical settings, opioid analgesics are commonly used in battlefield applications to ameliorate pain due to traumatic injuries. In battlefield settings, the stresses of battle can result in under or over dosing of patients, and overdosing can result in death. An opioid dosage form with controlled release features that are based on the individual's levels of opioid would be very advantageous in such systems.
There thus remains a need for compositions and methods for administering opioids and their antagonists that can be used to reduce the incidence of opioid toxicity.